3-methoxybutan-1-ol

Endpoint summary

Description of key information

There are sufficient data to assess the acute toxicity of 3-methoxybutan-1-ol and it is considered to have low acute toxicity by oral, inhalation and dermal routes of exposure. 

Additional information

The acute toxicity of 3-methoxybutan-1-ol was first reported in the 1930’s. A series of tests investigated its acute and subacute toxicity in several animal species following, for example, inhalation and subcutaneous routes of exposure.

Similar tests were conducted on 3 -methoxybutyl acetate, the putative rapidly and extensively formed proximate metabolite of which is 3 -methoxybutan-1-ol (see CSR Section 5.1), and indeed acute toxicity results reported for 3 -methoxybutan-1-ol are very similar to those for 3 -methoxybutyl acetate. Although these tests are poorly reported by modern standards, comparable results have been reported in several species and following different routes of exposure. In addition, some studies were repeated to guideline standards, the results of which are consistent with the earlier experimental toxicity studies for 3-methoxybutan-1-ol (Hoechst, 1991a). The key study is a guideline oral acute toxicity study reported by Hoechst, 1991a.

3-methoxybutan-1-ol

In a guideline acute toxicity study with male and female Wistar rats, 3-methoxybutan-1-ol was dosed orally, by gavage, at 2000 mg/kg in water. Animals were observed daily for 14 days and weighed at weekly intervals. On day 15, rats were killed and examined macroscopically). The LD50 of 3-methoxybutan-1-ol was reported to be >2000 mg/kg (Hoechst, 1991). This result is supported by an earlier report of an LD50, in mice, of about 3000 mg/kg (Hoechst, 1966).

Cats, rabbits and guinea pigs were exposed to 3-methoxybutan-1-ol saturated in air (concentration of 6.2mg/l; 6200mg/m3) for 1 hour and 6 hours. In the 6 hr experiment one cat showed only slight irritation/drowsiness for a short time and was later lively without symptoms as were guinea pigs and rabbits throughout (Hoechst, 1930a).

Other early studies reported low acute and subacute toxicity following subcutaneous administration of 3-methoxybutan-1-ol.  A 10% solution in water was injected under the skin of one guinea pig as a single dose of 0.1 g/kg, and under the skin of another guinea pig on six consecutive days (same dose). The animals did not display any clinical symptoms and there were no abnormal findings in the urine. The same treatment also did not harm rats. In addition, a single dose of 0.5 g/kg and 1 g/kg did not cause any symptoms in rats. Therefore although there are no dermal acute toxicity studies available, the results of these subcutaneous injection studies (Hoechst AG, 1930a) indicate that the dermal route is also likely to be characterised by low toxicity.

3-methoxybutyl acetate

Similar results were reported for 3 -methoxybutyl acetate in contemporary experiments using comparable experimental protocols. Various species including guinea pigs, cats and rabbits were exposed for 1 or 6 hours to 3 -methoxybutyl acetate saturated in air. In each study, no adverse clinical signs were reported, other than mild irritation. The concentration of 3 -methoxybutyl acetate in these experiments was about 10,000 mg/m3 (Hoechst, 1930a). In another early study, conducted and reported by Hoechst (1930b), 5 groups of mice were exposed for 2 hours to concentrations of 3 -methoxybutyl acetate (the putative major metabolite of which is 3-methoxybutan-1-ol) ranging from about 47,500 to 285,000 mg/m3. Following exposure (2 hours) at 142,500 mg/m³and at 190,000 mg/m³one animal of three died during the overnight post exposure period. At the highest dose, all animals survived.

Although these acute inhalation toxicity experiments are non-guideline studies, it appears that the LC50 (2 hour) for 3 -methoxybutyl acetate is likely to be at least 95,000 mg/m³. In addition as exposure for 6 hours to other species such as cats and rabbits to a concentration of 10,000 mg/m3 was reported to produce, at worst, mild irritation, it seems likely that the LC50 (6 hour) is likely to be greater than 20,000 mg/m³.

A 10% solution of 3 -methoxybutyl acetate in oil was injected under the skin of one guinea pig as a single dose of 0.1 g/kg, and under the skin of another guinea pig on six consecutive days (same dose). The animals did not display any clinical symptoms and no abnormal findings were found in the urine. The same treatment also did not harm rats. In addition, a single dose of 0.5 g/kg and 1 g/kg did not cause any clinical signs in rats (Hoechst, 1930a).

Systemic exposure of animals exposed to either 3 -methoxybutan-1ol or 3-methoxybutyl acetate is likely to be qualitatively and quantitatively similar, as 3 -methoxybutan-1 -ol is expected to be a rapidly and extensively formed metabolite of 3 -methoxybutyl acetate. Therefore the results of toxicity studies on either substance are relevant to the safety assessment of each. The diverse information above characterises these 2 materials as substances of low acute toxicity. By the inhalation route of exposure, although no guideline study is available, it is clear that the LC50 (4hr) for these substances is likely to be greater than 20,000 mg/m³. Similarly a guideline oral gavage administration study reported an LD50 greater than 2000mg/kg. The low systemic toxicity profile indicated by these routes of exposure is also consistent with the lack of findings following subcutaneous injection of 1000 mg/kg to rats, suggesting that acute toxicity by the dermal route is also likely to be characterized by low toxicity. Further acute toxicity investigations are considered scientifically unjustified.

Justification for classification or non-classification

According to criteria in Regulation (EC) No.1272/2008, the substance is not classified for acute toxicology. There are sufficient data available for 3-methoxybutan-1-ol to conclude that the substance does not warrant classification for acute toxicity via oral, inhalation or dermal routes of exposure.